Here we report the development of our Next Generation Automated Multiplexed Oligonucleotide Synthesizer (NG-1536-AMOS), capable of producing 1536 samples in a single run using a multi-well filtered titer plate. With the potential to synthesize up to 3456 samples per plate, we converted the BioRAPTR Flying Reagent Dispenser into an open-well system where spent reagents are drained to waste under vacuum. During synthesis, reagents are delivered on-the-fly to each micro-titer well at volumes ≤5 μl with plate speeds up to 150 mm/s. Using gas-phase cleavage and deprotection, a full plate of 1536 60 mers may be processed with same-day turnaround with an average yield per well at 3.5 nmol. Final product at only $0.00277/base is eluted into a low-volume collection plate for immediate use in downstream application (e.g. Biomek FX for versatile sample handling). Also, crude oligonucleotide quality is comparable to that of commercial synthesis instrumentation, with an error rate on the NG-1536-AMOS platform of 1.53/717 bases. Furthermore, mass spectral analysis on strands synthesized up to 80 bases showed high purity with an average coupling efficiency of 99.5%.

After a long developmental effort, we can now fabricate, using thin-film techniques, both rigid modiolar multielectrodes and flexible scala tympani multielectrodes which we believe appropriate for long-term implantation in human subjects. In vitro and in vivo life tests are in progress to confirm this expectation.

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It is possible to generate auditory percepts in profoundly deaf subjects through the direct electrical stimulation of the auditory nerve. To achieve auditory percepts having the complexity and information content of speech, it is necessary to stimulate separately a number of dIscrete subsets of fibers of the auditory nerve. Thin film electrodes fabricated through photolithographic techniques are attractive as stimulation microelectrode arrays because of the high dimensional resolution and good electrical and mechanical reproducibility of such electrodes. The requirements of survival of such arrays for decades in the biological environment have led us to use materials and techniques not typically handled photolithographically. Rigid electrode arrays have been developed using sapphire substrate tantalum conductors and tantalum pentoxide insulation. Flexible arrays have been developed using a polyimide-titanium-platinum-polyimide sandwich. These electrodes and their fabrication will be described.